In the past, dose responses results from in life toxicology studies were used to estimate no observed effect levels (NOELs) and more recently benchmark doses (BMDs). These observational studies of apical endpoints were frequently followed up by mechanistic studies both in intact animals and in in vitro models to determine modes of action (MOAs) and lend support to using either linear or threshold-based low dose extrapolations.  Over the past two decades, gene expression analysis …